Recognition of Impaired Atomoxetine Metabolism Because of Low CYP2D6 Activity

Ten out of 100 children treated for attention deficit hyperactivity disorder with standard doses of atomoxetine were selected by a neurologist for cytochrome P450 2D6 and cytochrome P450 209 genotyping, based on late response (>9 weeks) and adverse effects (gastrointestinal problems, sleeping disorders, malaise, inactivity, and mood instabilities). After genotyping, eight children were confirmed to have compromised cytochrome P450 2D6 activity because of at least one nonfunctional or less functional allele. Cytochrome P450 C19 is a minor pathway in atomoxetine metabolism and therefore of less importance. Tailored therapeutic advice was given to the neurologist. Four children with compromised cytochrome P450 2D6 activity responded better after decreasing their atomoxetine dose. The other four ceased treatment because of initial adverse effects. These cases indicate that compromised atomoxetine metabolism can be recognized, based on adverse effects and late response to atomoxetine. Physicians should be aware of the typical pattern of adverse effects and late response in atomoxetine treatment, possibly indicating compromised cytochrome P450 2D6 activity. Cytochrome P450 2D6 genotyping before atomoxetine treatment may be beneficial in preventing overdosing or early cessation. Further research is needed to establish the cost versus benefit ratio of prospective cytochrome P450 2D6 genotyping in atomoxetine treatment. (C) 2010 by Elsevier Inc. All rights reserved.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Recognition of Impaired Atomoxetine Metabolism Because of Low CYP2D6 Activity

Ten out of 100 children treated for attention deficit hyperactivity disorder with standard doses of atomoxetine were selected by a neurologist for cytochrome P450 2D6 and cytochrome P450 209 genotyping, based on late response (>9 weeks) and adverse effects (gastrointestinal problems, sleeping disorders, malaise, inactivity, and mood instabilities). After genotyping, eight children were confirmed to have compromised cytochrome P450 2D6 activity because of at least one nonfunctional or less functional allele. Cytochrome P450 C19 is a minor pathway in atomoxetine metabolism and therefore of less importance. Tailored therapeutic advice was given to the neurologist. Four children with compromised cytochrome P450 2D6 activity responded better after decreasing their atomoxetine dose. The other four ceased treatment because of initial adverse effects. These cases indicate that compromised atomoxetine metabolism can be recognized, based on adverse effects and late response to atomoxetine. Physicians should be aware of the typical pattern of adverse effects and late response in atomoxetine treatment, possibly indicating compromised cytochrome P450 2D6 activity. Cytochrome P450 2D6 genotyping before atomoxetine treatment may be beneficial in preventing overdosing or early cessation. Further research is needed to establish the cost versus benefit ratio of prospective cytochrome P450 2D6 genotyping in atomoxetine treatment. (C) 2010 by Elsevier Inc. All rights reserved

Further evaluation of quantitative nuclear image features for classification of lung carcinomas

The usefulness of quantitative nuclear image features (QNI) for the histological classification of lung carcinomas was investigated. As no clear distinction could be established between the distributions of these features for the nuclei of squamous cell, adenocarcinoma, and large cell carcinoma, the attention was restricted to the discrimination between small cell lung carcinoma (SCLC) and non-small cell carcinoma (NSCLC). This discrimination is the crucial one in discussions about the choice of treatment. The differences between SCLC and NSCLC are statistically highly significant for various QNI features. The use of more than one QNI feature hardly raised the discriminatory performance with respect to the distinction between SCLC and NSCLC. Inferences were made about the probability and confidence interval of SCLC for a given QNI feature. It is concluded that in cases of uncertainty or disagreement, nuclear characteristics are useful for the discrimination between SCLC and NSCLC

How can technology enhanced learning improve the efficiency and quality of help seeking and giving for programming

Programming tutorials are self-regulated learning activities where students are responsible for their own work pace and learning experience. They are working on programming assignments under supervision of teaching assistants (TAs), where help seeking is an essential skill. Especially, the ability to formulate specific questions contributes to higher test results. In addition, the likelihood of seeking help can be increased by electronic measures, as it is perceived as less threatening. During programming tutorials at the University of Twente the queue management system TA-help.me is used. In order to improve the quality of the learning process, this system was expanded by the following features: 1. Students had to choose a category to which their question belongs. 2. Students had to formulate their question or select a previously asked question. The extentions resulted from a Creative Technology Design process. For evaluation, quantitative data were gathered to measure the quality of the help seeking of students and the acceptance of the tool. Furthermore, TAs were interviewed to check if the tool improved the efficiency and quality of the help seeking and giving. The data indicate that the amount of improvident help seeking reduced, the categories were perceived as useful by the students. Furthermore, adding categories to the questions offered the TAs the opportunity to select topics and to spread their attention more effectively. Typing out the questions did, however, not increase the amount of more specific questions asked. Future research includes how to guide students to ask better questions

Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation A Randomized Clinical Trial

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